Koordiniert in:

Thema(en):

Aufruf zur Vorschlagseinreichung:

Finanzierungsprogramm:

ERC-SG - ERC Starting Grant

Ziel

Structural variation and copy-number variant regions (CNVs) (including segmental duplications) are usually underrepresented in genome analyses but are becoming a prominent feature in understanding the organization of genomes as well as many diseases. Large-scale comparative sequencing projects promised a golden era in the study of human evolution, however, many genome regions, especially these complicated regions, are clearly not solved.

Despite international efforts to characterize thousand of human genomes to understand the extent of structural variants in the human species, primates (our closest relatives) have somehow been forgotten. Yet, they are the ideal set of species to study the evolution of these features from both mechanistic and adaptive points of view. Most genome projects include only one individual as a reference but in order to understand the impact of structural variants in the evolution of every species we need to re-sequence multiple individuals of each species. We can only understand the origins of genomic variants and phenotypical differences among species if we can model variation within species and compare it to a proper perspective with the differences among species.

The object of this proposal is to discover the extent of genome structural polymorphism within the great ape species by generating next-generation sequencing datasets at high coverage from multiple individuals of diverse species and subspecies, characterizing structural variants and validating them experimentally. The results of these analyses will assess the rate of genome variation in primate evolution, characterize regional deletions and copy-number expansions as well as determine the patterns of selection acting upon them and whether the diversity of these segments is consistent with other forms of genetic variation among humans and great apes. In so doing, a fundamental insight will be provided into evolutionary variation of these regions among primates and into the mechanisms of disease-causing rearrangements with multiple repercussions in the understanding of evolution and human disease.